Straight Trippin'

In his 1968 novel The Electric Kool-Aid Acid Test, Tom Wolfe proclaimed that researchers conducting experiments with LSD ("those big fat letters") were living in a "fantasy," and that:

[The] fantasy was that the volunteers were laboratory animals that had to be dealt with objectively, quantitatively ... But the doctors were so out of it. They never took LSD themselves and they had absolutely no comprehension, and it couldn't be put into words anyway.

The concern would not last long. The Comprehensive Drug Abuse Prevention and Control Act of 1970 divided drugs into "schedules," or classes, on the basis of their potential for abuse, accepted medical use, and accepted safety under medical supervision. LSD, along with psilocybin, mescaline, peyote, and even cannabis, is now categorized as a Schedule I drug (the most severe classification), according to the Controlled Substances Act.

Fifty years after Tom Wolfe documented that epic LSD trip on a bus called "Further," a new breed of scientists is attempting once again to put Schedule I drugs into words (peer-reviewed ones, thankfully). This time, they might not be operating under a fantasy. The rigorous and careful exploration of these substances points to four key benefits.

First, potential new therapies. A team of researchers recently found encouraging results for MDMA (ecstasy, minus the nasty additives) in the treatment of posttraumatic stress disorder when used in conjunction with psychotherapy. In the era of two wars and scores of suffering soldiers, this is a noble pursuit. Studies such as these also underscore that successful treatment is not just a matter of popping some Molly, blasting The xx, and staring at the ceiling, but rather taking responsible doses of the stuff while sifting through memories and motivations with a mental health professional (though I imagine The xx helps; it usually does).

Another recent analysis of clinical trials on LSD concluded that the substance helped participants treat alcohol dependency. Investigators said that it was common "for patients following their LSD experience to become much more self-accepting, to show greater openness and accessibility, and to adopt a more positive, optimistic view of their capacities to face future problems." These drugs alone do not promise to solve our problems, but they might help get us to a place where we can.

Second, control and predictability. A troubling aspect of our psychology is that moments of happiness and enlightenment are all too often fleeting. The ability to induce empathy and self-awareness (among other desirable states) in a controlled environment offers the chance to bring about such effects deliberately -- rather than, say, disappearing into the Amazon, assuming Lotus pose, and hoping for the best.

Experiments with psilocybin (the "magic" in "magic mushrooms") recently found evidence that a little magic goes a long way with patients suffering from anxiety brought on by advanced-stage cancer. Other studies point to the efficacy of the funny fungi in treating obsessive-compulsive disorder. But psilocybin is best known for its mystical qualities and spiritual awakenings, and scientists have focused their lens on these squishier effects, as well.

Researchers in one study did find "increased measures of mystical experience," including "substantial personal meaning and spiritual significance" and reports of "sustained positive changes in attitudes and behavior." Obvious, perhaps, but these bright, self-affirming states deserve to be explored in the stable environment of the lab. Predictability, researchers argue, will enable more rigorous investigation into the causes and effects of metaphysical experiences. More visceral proponents might side instead with Ken Kesey, Wolfe's infamous tripper, who put it this way after a particularly inspired session: "You said it, bub, but like a lot of other people, you don't even know." Perhaps, they argue, we aren't meant to.

Third, new markets. The Multidisciplinary Association for Psychedelic Studies (MAPS), a self-described nonprofit research and educational organization focused on the careful uses of psychedelics and marijuana, is now undertaking a 10-year, $15-million plan to make MDMA into an FDA-approved prescription medicine. But many scientists doubt that these drugs will make it to market successfully, citing the complexity of the drug markets, the conflicted cultural and legal history surrounding Schedule I substances, and the regulatory challenges to their successful commercialization (a patent on MDMA, for example, might be wishful thinking).

That's a dealbreaker. Kesey reminds us that when "you've got something like we've got, you can't just sit on it. You've got to move off of it ... It only works if you bring other people into it." Depending on your interpretation of Keseyan economics, substances with promising benefits should either find their way into the broader ecosystem (creating the essential conditions for commercialization), or they should remain, legally or illegally, outside the domain of traditional pharmacology (crippling the prospect of profit, and hence the incentive for drug manufacturers).

"The current relationship between regulators and these Schedule 1 substances is a tangle of impossible possibilities," writes Tim Doody. Researchers, then, are left operating in the spaces between the law. One such space is a kind of "crowdsourced" science, in which individuals self-administer and self-report on the effects of substances that are difficult or illegal to test in the lab. Dr. James Fadiman, a veteran LSD researcher, recently set up such a study to test the effects of small "micro-doses" of LSD. The results, Doody quotes him as saying, seem to be stable and impressive: Many participants reportedly confirmed that their lives were noticeably easier, more focused, more productive -- in short, "a good day. That seems to be what we're discovering," he said.

Highly qualitative and in dire need of peer review, to be sure. But the evidence continues to emerge from these obscure corners of the community. That helps and hurts. Inspired researchers have an opportunity to carve out a space for creative and potentially groundbreaking analysis, but the constant scrutiny of regulators and the built-in skepticism of the scientific community more often move researchers to heed Wolfe's advice: "Haul ass, Kesey. Move. Scram. Split flee hide vanish disintegrate. Like run." It would be nice to see what would happen if they didn't.

Fourth, a reminder of the continued importance of good science. For all the evidence pointing to the benefits of Schedule I drugs, there is a great deal reminding us of the risks -- and so much more testing to do. In no way should we embrace Kesey's dismissal of reason ("Cassady doesn't have to think anymore") at the expense of solid answers. When it comes to Schedule I, side effects may include premature excitement.

But new deals in this space signal a shift in policy and the gradual opening of new markets. On June 12, KannaLife Sciences, a developmental stage phyto-medical and pharmaceutical company, successfully negotiated a license from the National Institutes of Health related to a method of treating diseases by administering a non-psychoactive cannabinoid. The agreement marked the successful transition of cannabinoid technology from the U.S. government to a small commercial enterprise, and the opportunity to design a novel drug candidate to treat the 1.5 million sufferers of hepatic encephalopathy. The license vindicated years of work on the innovative drug-development plan, application, and deal structure by co-founder and CEO Dean Petkanas, who is now working to solve a related problem: the regulation of the cannabis-packaging industry using a comprehensive standardization method designed by KannaLife co-founder Thoma Kikis. The team estimates that standardization, which is essential to safe and scalable cannabis distribution, is a $1.4-billion opportunity.

And so we have to ask the question that Wolfe posed in his book: "Do you suppose this is the -- new wave...?"